NEURO/IMMUNE INTERACTION IN OCULAR SYSTEM

眼系统中的神经/免疫相互作用

• 批准号: 2019983
• 负责人: H KATHLEEN DANNELLY
• 金额: $ 3.33万
• 依托单位: INDIANA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2019983
• 关键词: B lymphocyte; T lymphocyte; acetylcholinesterase; antibody formation; antigen antibody reaction; biological information processing; cell type; choline acetyltransferase; cytokine; enzyme activity; enzyme linked immunosorbent assay; eye; homeostasis; immunocytochemistry; laboratory mouse; model design /development; neuroimmunomodulation; parasympathetic nervous system; plaque assay; secretory immune system; statistics /biometry

DESCRIPTION: (Adapted from applicant's abstract) The objective of the proposed research is to develop a model system for studying interaction between the immune and nervous systems. Such interactions normally helps maintain both the physiological and behavioral components of homeostasis throughout the body. Previous studies in avian species indicated that parasympathetic and sympathetic nerve fibers serve a role in modulation of lymphocyte activity and consequently influence the secretory immune system. Whether manipulation of the immune system exerts reciprocal modulatory effects on the nervous system is currently unknown. This investigation aims to establish whether changes introduced through the immune system influence the parasympathetic division of the autonomic nervous system (ANS) with the eye of mouse as the experimental model. Preliminary studies indicate that modulation of cholinergic enzyme activity is induced primarily by T cell-dependent antigens. This may be due to the mobilization of T and/or accessory cells elaborating cytokines in the process. Subsequent experiments will explore effects of T cell- independent antigens on immunity and cholinergic neural activity. Mice will be immunized with antigen applied either topically on the eye or intraperitoneally. Thus, localized changes in the lacrimal gland and conjunctiva will be examined by immunohistochemistry to detect antibody production and lymphoid cell migration in conjunction with changes in acetylcholinesterase (AChE, EC 3.1.1.7) and choline acetyltransferase (ChAT, EC 2.3.1.6). B cells secreting specific antibody will be localized in mouse ocular tissues by plaque forming cell assay. The role of T and accessory cells will be evaluated un in vitro conditions by assessing the actions of cytokines on tissue cholinergic enzymes. Antibody production in circulation is assessed in individual mice by enzyme-linked immunosorbent assays. AChE and ChAT will be determined by radiometric assays. Brain and spleen serve as controls for ocular tissues, to distinguish the overall physiological changes that may accompany regional antigen application. This study will lend support to the hypothesis that secretory immunity and the ANS communicate bi- directionally to prevent host infections and maintain homeostasis.

描述：(改编自申请者的摘要) 建议的研究是开发一个研究交互的模型系统 在免疫系统和神经系统之间。这样的互动通常会有所帮助 维持动态平衡的生理和行为成分 遍及全身。以前对鸟类的研究表明， 副交感神经纤维和交感神经纤维在调制中起作用 影响淋巴细胞活性，从而影响分泌性免疫 系统。 免疫系统的操纵是否起到相互调节的作用 对神经系统的影响目前尚不清楚。这项调查 旨在确定通过免疫系统引入的变化 影响自主神经系统的副交感神经分裂 (ANS)以小鼠眼部为实验模型。初步 研究表明，胆碱能酶活性的调节是 主要由T细胞依赖抗原诱导。这可能是由于 T细胞和/或辅助性细胞因子的动员 进程。随后的实验将探索T细胞- 独立抗原对免疫和胆碱能神经活性的影响。老鼠 会用抗原免疫，局部涂在眼睛或 在腹膜内。因此，泪腺和泪腺的局限性变化 结膜进行免疫组织化学检查以检测抗体。 生产和淋巴样细胞迁移与细胞周期的变化 乙酰胆碱酯酶(AChE，EC 3.1.1.7)和胆碱乙酰转移酶 (Chat，EC 2.3.1.6)。分泌特异性抗体的B细胞将是 空斑形成细胞实验定位于小鼠眼部组织。这个 T细胞和辅助细胞的作用将在体外条件下进行评估 通过评估细胞因子对组织胆碱能酶的作用。 循环中抗体的产生是通过以下方法评估的： 酶联免疫吸附试验。疼痛和聊天将被确定 通过放射分析。脑和脾是眼部的控制点 组织，以区分可能发生的整体生理变化 伴随局部抗原应用。这项研究将提供支持 关于分泌免疫和ANS传递双向免疫信号的假设 方向性地防止宿主感染和维持内环境平衡。